The present invention relates generally to the evaluation of cardiac patients in order to assess their risk for future ischemic heart events.
Presently, it is known that many proteins are associated with ischemic heart events. One of the earliest proteins to show a relationship with ischemic heart events is creatine kinase, hereinafter referred to as CK. Since 1962, blood tests for total CK enzyme activity have been used in the diagnosis and estimation of the severity of myocardial infarcts. Since the 1970's, it has been known that one particular isoenzyme form of CK, i.e. CK-MB, is released into the blood stream following a myocardial infarct. In addition, other proteins have been associated with myocardial infarction including serum glutamic oxylotransamenase (SGOT), lactic dehydrogenase (LDH), isocitric dehydrogenase, haptoglobin, alpha-l-acid glycoprotein, antitrypsin, C-reactive protein, and fibrinogen.
CK activity and CK-MB activity have also been related to the size of the infarct (Shell et al, Sensitivity and Specificity of MB-Creatine Kinase Activity Determined with Column Chromatography, Am. J. Cardiol., 44: 67, 1979, and Shell et al, Quantitative Assessment of the Extent of Myocardial Infarction in the Conscious Dog by Means of Analysis of Serial Changes in Serum Creatine Phosphokinase Activity, J. Clin. Invest. 50: 2614, 1971). It is generally accepted by those skilled in the art that patients admitted to rule out myocardial infarction experience a 10-12% one year mortality rate regardless of the results of total CK enzyme testing, with no ability to segregate patients with varying degrees of risk. According to Smith, et al., Clin Chim Acta 81: 75-85 (1977), a quantitative relationship with enzymatic infarct size also exists for alpha-l-acid glycoproteins.
While the aforedescribed proteins may be useful in determining whether an individual has suffered a recent myocardial infarction or in assisting physicians in ascertaining the size of that infarct, none of these proteins have been shown to have any significant predictive correlation to future ischemic events--future myocardial infarction, future unstable angina pectoris or future sudden cardiac-associated death. Prediction of the probability of future ischemic events is a major problem for individual patients since undue treatment could be avoided, if the patients could be identified who are at low risk. Alternatively, patients who would be amenable to therapy would also be identified.
Consequently, there exists a great need for a diagnostic test which will allow physicians to specifically determine whether a cardiac patient is at risk of experiencing a future ischemic event in order that therapy can be employed to prevent or mitigate such subsequent events. The present invention satisfies this need.